Production and separation of ⁴³Sc for radiopharmaceutical purposes

The favorable decay properties of ⁴³Sc and ⁴⁴Sc for PET make them promising candidates for future applications in nuclear medicine. An advantage ⁴³Sc (T_1/2 = 3.89 h, Eβ⁺_av = 476 keV [88%]) exhibits over ⁴⁴Sc, however, is the absence of co-emitted high energy γ-rays. While the production and application of ⁴⁴Sc has been comprehensively discussed, research concerning ⁴³Sc is still in its infancy. This study aimed at developing two different production routes for ⁴³Sc, based on proton irradiation of enriched ⁴⁶Ti and ⁴³Ca target material.

⁴³Sc was produced via the ⁴⁶Ti(p,α)⁴³Sc and ⁴³Ca(p,n)⁴³Sc nuclear reactions, yielding activities of up to 225 MBq and 480 MBq, respectively. ⁴³Sc was chemically separated from enriched metallic ⁴⁶Ti (97.0%) and ⁴³CaCO₃ (57.9%) targets, using extraction chromatography. In both cases, ~90% of the final activity was eluted in a small volume of 700 μL, thereby, making it suitable for direct radiolabeling. The prepared products were of high radionuclidic purity, i.e. 98.2% ⁴³Sc were achieved from the irradiation of ⁴⁶Ti, whereas the product isolated from irradiated ⁴³Ca consisted of 66.2% ⁴³Sc and 33.3% ⁴⁴Sc. A PET phantom study performed with ⁴³Sc, via both nuclear reactions, revealed slightly improved resolution over ⁴⁴Sc. In order to assess the chemical purity of the separated ⁴³Sc, radiolabeling experiments were performed with DOTANOC, attaining specific activities of 5-8 MBq/nmol, respectively, with a radiochemical yield of >96%.

It was determined that higher ⁴³Sc activities were accessible via the ⁴³Ca production route, with a comparatively less complex target preparation and separation procedure. The product isolated from irradiated ⁴⁶Ti, however, revealed purer ⁴³Sc with minor radionuclidic impurities. Based on the results obtained herein, the ⁴³Ca route features some advantages (such as higher yields and direct usage of the purchased target material) over the ⁴⁶Ti path when aiming at ⁴³Sc production on a routine basis.